1. Field of the Invention
The present invention relates to a medical device; more particularly, this invention relates to methods of sterilizing the medical device by irradiation of the medical device.
2. Background of the Invention
Systems for sterilizing products such as food or mail to remove harmful micro-organisms are known in the art. Such a system may operate as a conveyor in which products are carried pass a radiation source where the product is subjected to a predetermined dose of radiation, e.g., X-ray, gamma or electron radiation, at a predetermined level or intensity. Careful and continuous control of the dose delivered to a product is critical. If a product receives too little radiation, the desired sterilization, pasteurization, and/or chemical modification is not obtained. If a product receives too much radiation, the treatment is damaging to the product.
It is known to expose a product to two passes before a radiation source to ensure adequate sterilization, or rotating the product within the radiation field. U.S. Pat. No. 6,806,476 discloses a radiation conveyor system operated to cause a product on the conveyor to make two passes before the radiation source, e.g., an electron beam. The product is flipped 180 degrees between first and second passes. The system exposes the product to a predetermined level of radiation defined by, among other things, a dose level, beam width, speed of conveyor selected and electron energy spread spectrum.
For products that are particularly dense, the art has configured systems, such as the one described in U.S. Pat. No. 6,806,476, to perform two passes before the radiation source. The first pass may place the product broad side before the radiation source. Then the product is flipped 180 degrees around and again passed broad side before the radiation source. This ensures a minimum dosage level is applied to the product to ensure sterility. The same dose level is used for both passes.
Sterilization of implantable medical devices by exposure to radiation is known. Sterilization is typically performed on implantable medical devices, such as stents and catheters, to reduce the bioburden on the device. Bioburden refers generally to the number of microorganisms that contaminate an object. The degree of sterilization is typically measured by a Sterility Assurance Level (“SAL”), referring to the probability of a viable microorganism being present on a device unit after sterilization. A sterilization dose can be determined by selecting a dose that provides a required “SAL”. The required SAL for a device is dependent on the intended use of the device. For example, a device to be used in the body's fluid path is considered a Class III device. SALs for various medical devices can be found in materials from the Association for the Advancement of Medical Instrumentation (AAMI) in Arlington, Va. For example, the SAL for biodegradable stents is at a radiation dose from about 20 kGy to about 30 kGy. The required dosage depends upon the starting bioburden in the medical device, which can vary based on the degree of sterility maintained when the medical device is fabricated.
Medical devices composed in whole or in part of polymers can be sterilized by various kinds of radiation, including, but not limited to, electron beam (e-beam), gamma ray, ultraviolet, infra-red, ion beam, and x-ray sterilization. A sterilization dose can be determined by selecting a dose that provides a required SAL. One problem faced in the art is how to apply sufficient radiation to achieve the SAL without causing degradation to bio-absorbable polymers and/or therapeutic agents contained within a polymer coating. High-energy radiation tends to produce ionization and excitation in polymer molecules, as well as free radicals. These energy-rich species undergo dissociation, abstraction, chain scission and cross-linking in a sequence leading to chemical stability. The stabilization process can occur during, immediately after, or even days, weeks, or months after irradiation which often results in physical and chemical cross-linking or chain scission. Resultant physical changes can include embitterment, discoloration, odor generation, stiffening, and softening, among others. In particular, the deterioration of the performance of polymeric materials and drugs due to e-beam radiation sterilization has been associated with free radical formation in a device during radiation exposure and by reaction with other parts of the polymer chains. The reaction is dependent on, e.g., e-beam dose and level of temperature.
For these reasons, sterilization procedures for medical devices containing polymers and/or radiation-sensitive drugs specify an upper limit to the dose levels that the medical device may accept without degrading the performance of the product. As the actual upper limit to ensure the medical device does not degrade, or lower limit to ensure sterility is an approximation, the lower dose range and upper dose range often includes safety factors, which narrows the operating range for sterilization. This complicates the sterilization process and limits the range of designs or materials available for medical devices.
Accordingly, there is a continuing need for improvement in the processes for sterilization of medical devices containing polymers and/or therapeutic drugs that are adversely affected by over-exposure to radiation.